A plant-derived compound for more effective and less expensive gene therapy

Making an effective and inexpensive treatment to cure genetic diseases is on the right track. Gene therapy could hold the key to recovery for people with immune system deficiencies and blood conditions, such as leukemia and sickle cell disease. For a long time, such diseases required a bone marrow transplant, but they can now be treated by modifying the blood stem cells of patients, which corrects the genetic abnormality at the source of the disease. The problem is that few people can afford such a treatment, which is long and expensive. Many steps are required to implant healthy genes into patients’ blood stem cells. However, scientists at Scripps Research in California believe that this expensive and time-consuming system can be replaced with an effective, efficient and economical method of gene transfer. They detailed their research in an article in the american magazine Blood.

Their research revolves around caraphenol A, an anti-inflammatory compound closely related to resveratrol, a plant molecule found in grapes, red wine and other plants such as blackberries and peanuts. Like caraphenol A, resveratrol is also anti-inflammatory.

The team studied the chemical properties of resveratrol and similar compounds to see if viral vectors could be delivered easily into the blood. These vectors, used in gene therapy, would be important because stem cells, especially hematopoietic stem cells (immature cells that can develop into any type of blood cell like white blood cells, red blood cells and platelets), have multiple levels of virus protection. Therefore, hematopoietic stem cells, also called blood stem cells, are difficult to infiltrate. According to Bruce Torbett, associate professor in the Department of Immunology and Microbiology at the California campus, “Hemopoietic stem cell gene therapy is a double-deal.” During this research, the team found a way to make the treatment more reliable and effective.

Therapy and the bottleneck

Currently, a tiny fraction of hematopoietic stem cells are isolated from patients’ blood for treatment. For the purposes of the experiment, healthy genes are transmitted to stem cells using “lentiviral vectors”, viruses specially designed for this use. If the researchers used this technique, it is because they know that viruses have a natural tendency to “parasitize” the living cells around them. To defend themselves against what they consider to be an intrusion, hematopoietic stem cells protect themselves by triggering a reaction from their immune system. Because of this protection, it takes many attempts to get the genes into the blood stem cells, which also increases the cost of treatment.

Bruce Torbett, who led the study, found that adding caraphenol A to blood stem cells, mixed with lentiviral vectors, lowered cellular defenses, thus opening up easier access to vectors. When stem cells treated in this way are placed in mice, they divide with the new genetic information, saving valuable time. According to him, the more stem cells are matured and manipulated outside the body, the more likely they are to lose their ability to self-generate and heal disease.

The fact that most diseases treated with gene therapy affect children gave Bruce Torbett and his team a sense of urgency to carry out this research. They study the reasons for stem cell resistance to genetic modification with the aim of improving treatment outcomes while saving money.

Although the field of gene therapy has been evolving rapidly for decades, success has not always been there, due to the difficulty of introducing new and working genes into cells. After infiltration, the gene must then be activated and then remain so. Knowing that cells shut down genes that are too active or have unusual behavior is a new challenge to take on.